Remdesivir is an investigational drug that has demonstrated broad-spectrum antiviral activity against filoviruses (Ebola viruses, Marburg virus), coronaviruses (SARS-CoV, MERS-Co-V, SARS-CoV-2), paramyxoviruses (parainfluenza type III virus, Nipah virus, Hendra virus, measles, and mumps virus), and Pnemoviridae (respiratory syncytial virus).[1][2][3] 

Based on preliminary findings of a double-blind, randomized placebo-controlled trial that utilized the use of intravenous remdesivir in adults hospitalized with COVID-19, the U.S. Food and Drug Administration(FDA) issued an initial emergency use authorization(EUA) on May 1, 2020, to permit the use of remdesivir for treatment of adults and pediatric patients hospitalized with severe suspected or laboratory-confirmed COVID-19 infection with severity being defined as SpO2</= 94% on room air requiring supplemental oxygen, mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO).[4] 

However, on August 28, 2020, the FDA  broadened the scope of the existing EUA for remdesivir by permitting the use of remdesivir in all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 regardless of the severity of their illness. Based on its in vitro activity against SARS-CoV-2, multiple randomized clinical trials(RCTs) of parenteral remdesivir in mild to moderate and severe COVID-19 illness are currently ongoing in the USA and around the world. 

Remdesivir (GS-5734) is a phosphoramidite prodrug of a monophosphate nucleoside analog (GS-441524) and acts as a viral RNA-dependent RNA polymerase(RdRp) inhibitor, targeting the viral genome replication process.[5][6] 

Theoretically, nucleoside analogs do not permeate through the cell wall easily. Upon their subsequent entry into the host cell, they require phosphorylation to produce nucleoside triphosphate (NTP), which resembles adenosine triphosphate (ATP) and can be used by the RdRp enzymes or complexes for genome replication.[7][8][9] 

Once remdesivir is metabolized by the host cells into its pharmacologic active analog adenosine triphosphate (GS-443902), it competes with ATP for integration by the RdRp complex into the nascent RNA strand and, upon subsequent incorporation of a few more nucleotides, results in termination of RNA synthesis.[7][6]

Based on the review of the summary describing the compassionate use of remdesivir published by the European Medicines Agency (EMA,2020), researchers noted that the bioavailability of remdesivir in animal models was poor by oral route due to almost complete first-pass clearance attributed to poor hepatic stability. Also, the pharmacologic active analog adenosine triphosphate was delayed when administered via the intramuscular (IM) route. However, radiolabeled remdesivir administered intravenously in rats and monkeys demonstrated the widespread distribution of radioactivity in most tissues with the circulation of the predominant metabolite GS-441524. Hence, the conclusion was that the intravenous (IV) administration of remdesivir delivered the active metabolite rapidly compared to IM or oral route.

The recommended dose of remdesivir for adults and pediatric patients hospitalized with suspected or laboratory-confirmed COVID-19 infection is weight-based, and administration is via the IV route.

• Adults and pediatric patients weighing 40 kg and higher: 200 mg IV as a loading dose on day 1, followed by 100 mg IV daily for up to 9 additional days. 
• Pediatric patients weighing 3.5 kg to less than 40 kg: Single loading dose of 5 mg/kg on Day 1 followed by 2.5 mg/kg once daily from Day 2.

Remdesivir has no authorization for use in a non-hospital setting, and the optimal treatment duration for COVID-19 is unknown.

Considering that remdesivir is currently considered an investigational drug, its safety profile has not yet been fully characterized. Based on a review of available literature, the following are the possible organ-based adverse effects reported using remdesivir.[4][10][11][12][13][14][15][16]

• Cardiovascular: Hypotension, arrhythmias, and cardiac arrest
• Pulmonary: Dyspnea, Acute respiratory failure, acute respiratory distress, pneumothorax, pulmonary embolism
• Hematological: Anemia, lymphopenia
• Endocrine: Hyperglycemia
• Infectious: Pneumonia, septic shock
• Gastrointestinal: Nausea, vomiting, diarrhea, constipation, poor appetite, gastroparesis, and lower GI bleeding 
• Hepatic: increase in serum transaminases (ALT and/or AST), hyperbilirubinemia
• Renal and Metabolic: Acute kidney injury or worsening of underlying chronic kidney disease, hypernatremia, hypokalemia
• Neurological: Headache, lightheadedness
• Skin: Rash
• Psychiatric: Delirium
• Other adverse effects: Pyrexia, insomnia,multi-organ dysfunction, DVT, and hypersensitivity/anaphylactic reactions related to the infusion

Based on the guidance from the documentation published by the European Medicines Agency (EMA, 2020) and U.S FDA issued EUA, remdesivir is contraindicated in the following clinical situations unless the potential benefit of use of remdesivir outweighs the potential risks:

• Patients with alanine aminotransferase (ALT) levels >5-times upper limit of normal or severe hepatic dysfunction
• Adult and pediatric patients (>28 days old) with severe renal impairment described as eGFR < 30 ml/min
• Neonates (at least 7 days to ≤ 28 days old) with serum creatinine ≥1 mg/dL